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Estrogen in the Brain Prevents Obesity, Glucose Intolerance in Menopause

Published: 7/18/2017

Researchers at the University of Cincinnati (UC) have found
that adding estrogen in the brain may improve metabolic health in
obese females.

The study conducted by Christina Estrada, a doctoral candidate
in the UC psychology graduate program in the laboratory of Matia
Solomon, PhD, an associate professor in the UC Department of
Psychiatry and Behavioral Neuroscience, used animal models with
menopause (surgically-induced) to induce obesity. The findings will
be presented this week at the annual meeting of the Society for the
Study of Ingestive Behavior (SSIB), the leading society for
research encompassing all aspects of eating and drinking
behavior.

"We know as women age and enter into menopause, they tend to
gain body weight and body fat, particularly in the abdominal or
‘belly’ area. Excess abdominal fat greatly increases
risk for cardio-metabolic diseases,” says Solomon. "While
there are likely many factors that are associated with these risks
in menopausal women, estrogen loss is associated with body weight
and fat gain during menopause. In fact, estrogen treatment can
offset this weight gain in many women. For decades, we have known
that estrogen regulates energy balance in brain areas like the
hypothalamus. Many people don’t think about the brain as a
regulator of body weight; however, overall metabolic health is
maintained by crosstalk between the brain and the
body.”

Because in the brain, the medial amygdala (MeA) regulates body
weight and contains an abundance of estrogen receptors (molecules
that respond to estrogen), the researchers focused their attention
on the MeA as a target area to prevent metabolic risk factors,
commonly associated with menopause. The researchers used an animal
model of surgical menopause by removing the ovaries and delivered
estrogen directly in the MeA. Compared to placebo, estrogen
treatment in the MeA prevented weight and abdominal fat gain and
improved glucose tolerance in models without ovaries, suggesting
this region is as an important target for the estrogen-mediated
effects on metabolic health in menopausal females.

"Obesity is a national epidemic and women are becoming obese
at younger ages. Given the beneficial effects of estrogen on
metabolic health, we were interested in determining the
consequences of obesity on estrogen-related endpoints … akin
to younger, premenopausal women,” says Estrada. A separate
group of female animal models with intact ovaries were placed on a
high-fat diet. Relative to their lean counterparts, obese females
had increased blood estrogen levels, irregular reproductive cycles
and altered estrogen receptor expression in brain regions
regulating metabolic function including the hypothalamus and
MeA.

These findings suggest obesity may dampen the metabolically
beneficial effects of estrogen in the body and in the brain in
females.

"These findings are particularly important because we know
very little about the impact of obesity on brain function in
women,” Estrada says, adding that the research team believes
understanding how the brain and body work together to regulate
metabolic health offers a more holistic perspective of how to
tackle obesity prevention in women. The researchers say more
studies are needed to address this, and the team is focused on
understanding how obesity impacts brain health in females and
whether these changes are temporary or permanent.